Abstract OBJECTIVE: Our aim was to determine whether Lactobacillus rhamnosus GG (LGG) relieves symptoms in children with recurrent abdominal pain. PATIENTS AND METHODS: A total of 141 children with irritable bowel syndrome (IBS) or functional pain were enrolled in 9 primary care sites and a referral center. Children entered a randomized, double-blind, placebo-controlled trial and received LGG or placebo for 8 weeks and entered follow-up for 8 weeks. The primary outcome was overall pain at the end of the intervention period. At entry and at the end of the trial, children underwent a double-sugar intestinal permeability test. RESULTS: Compared with baseline, LGG, but not placebo, caused a significant reduction of both frequency (P < .01) and severity (P < .01) of abdominal pain. These differences still were significant at the end of follow-up (P < .02 and P < .001, respectively). At week 12, treatment success was achieved in 48 children in the LGG group compared with 37 children in the placebo group (P < .03); this difference still was present at the end of follow-up (P < .03). At entry, 59% of the children had abnormal results from the intestinal permeability test; LGG, but not placebo, determined a significant decrease in the number of patients with abnormal results from the intestinal permeability testing (P < .03). These effects mainly were in children with IBS. CONCLUSIONS: LGG significantly reduces the frequency and severity of abdominal pain in children with IBS; this effect is sustained and may be secondary to improvement of the gut barrier.

accettato per pubblicazione su Pediatrics. Title: A Randomized Controlled Trial of Lactobacillus Rhamnosus Strain GG in Children with Functional Abdominal Pain Authors: Francavilla, Ruggiero; Miniello, Vito; Magistà, Anna Maria; De Canio, Angela; Bucci, Nunzia; Castellaneta, Stefania; Lionetti, Elena; Indrio, Flavia; Peccarisi, Lucia; Gagliardi, Francesca; Polimeno, Lorenzo; Cavallo, Luciano Dear Dr. Francavilla: Thank you for your revised manuscript, which has been accepted by Pediatrics. All accepted papers are published online at www.pediatrics.org, which is the journal of record. The online publication date for your paper is not known at this time. Page proofs will be sent to you shortly before publication. Your paper could also be selected for print publication, but that decision will be made at a later date. Thank you for submitting your manuscript to Pediatrics and congratulations on its acceptance. Sincerely, Lewis R. First, MD Editor-in-Chief Ped...

Augmenter of Liver Regeneration (Alrp) enhances, through unknown mechanism/s, hepatocyte proliferation only when administered to partially hepatectomized (PH) rats. Liver resection, besides stimulating hepatocyte proliferation, induces reactive oxygen species (ROS), triggering apoptosis. To clarify the role of Alrp in the process of liver regeneration, hepatocyte proliferation, apoptosis, ROS-induced parameters and morphological findings of regenerating liver were studied from PH rats Alrp-treated for 72 h after the surgery. The same parameters, evaluated on regenerating liver from albumin-treated PH rats, were used as control. The results demonstrated that Alrp administration induces the anti-apoptotic gene expression, inhibits hepatocyte apoptosis and reduces ROS-induced cell damage. These and similar data from in vitro studies and the presence of 'Alrp homologous proteins' in viruses as well as in mammals (i) allow to hypothesize that Alrp activity/ies may not be exclusive for regenerating liver and (ii) suggest the use of Alrp in the treatment of oxidative stress-related diseases.

OBJECTIVES: The possible autoimmune involvement of the pituitary gland in patients with celiac disease (CD) has been suggested but demonstrated in only a few patients on gluten-free diet. We aimed to assess the prevalence and clinical meaning of anti-pituitary antibodies (APA) in children and adolescents with the newly diagnosed CD. METHODS: A total of 119 patients with CD (0.9-15.8 years old) attending the inpatient clinic of University Hospital were recruited for the cross-sectional study. Their height, weight, and body mass index (BMI) were recorded, and insulin-like growth factor-1 (IGF-1) and APA were assayed. APA was also determined in 98 sex- and age-matched controls. RESULTS: APA were detected in 50 patients (42.0%), 15 of them with high titer (30%) and 35 with low titer (70%), and in 2 control subjects at low titer (2%) (P<0.001). IGF-1 was higher in patients with negative than with low titer (P=0.02) or high titer APA (P=0.03). Height was more reduced in high-titer APA patients than in the negative ones (P<0.01). Height was positively correlated with IGF-1 (P<0.01) and negatively with chronological age (P=0.001). IGF-1 was positively correlated with BMI (P<0.001). For height prediction the regression analysis showed the rank order 1 for chronological age and 2 for IGF-1. CONCLUSIONS: In this paper we have shown a remarkable prevalence of positive APA in newly diagnosed CD patients. High APA titers are associated with height impairment, likely mediated by a reduction of IGF-1, thus suggesting that autoimmune pituitary process could induce a linear-growth impairment.

OBJECTIVE: To describe the clinical, serologic, and histologic characteristics of children with gluten sensitivity (GS). STUDY DESIGN: We studied 15 children (10 males and 5 females; mean age, 9.6 ± 3.9 years) with GS who were diagnosed based on a clear-cut relationship between wheat consumption and development of symptoms, after excluding celiac disease (CD) and wheat allergy, along with 15 children with active CD (5 males and 10 females; mean age, 9.1 ± 3.1 years) and 15 controls with a functional gastrointestinal disorder (6 males and 9 females; mean age, 8.6 ± 2.7 years). All children underwent CD panel testing (native antigliadin antibodies IgG and IgA, anti-tissue transglutaminase antibody IgA and IgG, and anti-endomysial antibody IgA), hematologic assessment (hemoglobin, iron, ferritin, aspartate aminotransferase, erythrocyte sedimentation rate), HLA typing, and small intestinal biopsy (on a voluntary basis in the children with GS). RESULTS: Abdominal pain was the most prevalent symptom in the children with GS (80%), followed by chronic diarrhea in (73%), tiredness (33%), bloating (26%), limb pain, vomiting, constipation, headache (20%), and failure to thrive (13%). Native antigliadin antibodies IgG was positive in 66% of the children with GS. No differences in nutritional, biochemical, or inflammatory markers were found between the children with GS and controls. HLA-DQ2 was found in 7 children with GS. Histology revealed normal to mildly inflamed mucosa (Marsh stage 0-1) in the children with GS. CONCLUSION: Our findings support the existence of GS in children across all ages with clinical, serologic, genetic, and histologic features similar to those of adults.

Background: Epidemiology of celiac disease (CD) is increasing. CD mainly presents in early childhood with small intestinal villous atrophy and signs of malabsorption. Compared to healthy individuals, CD patients seemed to be characterized by higher numbers of Gram-negative bacteria and lower numbers Gram-positive bacteria. Results: This study aimed at investigating the microbiota and metabolome of 19 celiac disease children under gluten-free diet (treated celiac disease, T-CD) and 15 non-celiac children (HC). PCR-denaturing gradient gel electrophoresis (DGGE) analyses by universal and group-specific primers were carried out in duodenal biopsies and faecal samples. Based on the number of PCR-DGGE bands, the diversity of Eubacteria was the higher in duodenal biopsies of T-CD than HC children. Bifidobacteria were only found in faecal samples. With a few exceptions, PCRDGGE profiles of faecal samples for Lactobacillus and Bifidobacteria differed between T-CD and HC. As shown by culture-dependent methods, the levels of Lactobacillus, Enterococcus and Bifidobacteria were confirmed to be significantly higher (P = 0.028; P = 0.019; and P = 0.023, respectively) in fecal samples of HC than in T-CD children. On the contrary, cell counts (CFU/ml) of presumptive Bacteroides, Staphylococcus, Salmonella, Shighella and Klebsiella were significantly higher (P = 0.014) in T-CD compared to HC children. Enterococcus faecium and Lactobacillus plantarum were the species most diffusely identified. This latter species was also found in all duodenal biopsies of T-CD and HC children. Other bacterial species were identified only in T-CD or HC faecal samples. As shown by Randomly Amplified Polymorphic DNA-PCR analysis, the percentage of strains identified as lactobacilli significantly (P = 0.011) differed between T-CD (ca. 26.5%) and HC (ca. 34.6%) groups. The metabolome of T-CD and HC children was studied using faecal and urine samples which were analyzed by gas-chromatography mass spectrometry-solid-phase microextraction and 1H-Nuclear Magnetic Resonance. As shown by Canonical Discriminant Analysis of Principal Coordinates, the levels of volatile organic compounds and free amino acids in faecal and/or urine samples were markedly affected by CD. Conclusion: As shown by the parallel microbiology and metabolome approach, the gluten-free diet lasting at least two years did not completely restore the microbiota and, consequently, the metabolome of CD children. Some molecules (e.g., ethyl-acetate and octyl-acetate, some short chain fatty acids and free amino acids, and glutamine) seems to be metabolic signatures of CD.

This study aimed at investigating the fecal microbiota and metabolome of children with Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and autism (AD) in comparison to healthy children (HC). Bacterial tag-encoded FLX-titanium amplicon pyrosequencing (bTEFAP) of the 16S rDNA and 16S rRNA analyses were carried out to determine total bacteria (16S rDNA) and metabolically active bacteria (16S rRNA), respectively. The main bacterial phyla (Firmicutes, Bacteroidetes, Fusobacteria and Verrucomicrobia) significantly (P<0.05) changed among the three groups of children. As estimated by rarefaction, Chao and Shannon diversity index, the highest microbial diversity was found in AD children. Based on 16S-rRNA and culture-dependent data, Faecalibacterium and Ruminococcus were present at the highest level in fecal samples of PDD-NOS and HC children. Caloramator, Sarcina and Clostridium genera were the highest in AD children. Compared to HC, the composition of Lachnospiraceae family also differed in PDD-NOS and, especially, AD children. Except for Eubacterium siraeum, the lowest level of Eubacteriaceae was found on fecal samples of AD children. The level of Bacteroidetes genera and some Alistipes and Akkermansia species were almost the highest in PDD-NOS or AD children as well as almost all the identified Sutterellaceae and Enterobacteriaceae were the highest in AD. Compared to HC children, Bifidobacterium species decreased in AD. As shown by Canonical Discriminant Analysis of Principal Coordinates, the levels of free amino acids and volatile organic compounds of fecal samples were markedly affected in PDD-NOS and, especially, AD children. If the gut microbiota differences among AD and PDD-NOS and HC children are one of the concomitant causes or the consequence of autism, they may have implications regarding specific diagnostic test, and/or for treatment and prevention.

This retrospective multicentre study aims to evaluate the clinical and epidemiological features of HCV infection in a cohort of immigrants in Italy. Tests were carried out on 194 HCV positive subjects, who represented 5.7% of the participants at baseline screening: the virological (viral load, genotype) and biochemical appearance of their infection was determined, and the disease was staged by histological examination in the patients who had indicated their willingness. Standard therapy (peg-interferon + ribavirin) was implemented in patients who agreed to undergo treatment. The majority of immigrants were of East-European origin (48.4%), females were globally slightly predominant and the average age was 41.4 years. Of the 194 patients, 119 (63.1%) proved to be viraemic: genotype 1 was the most frequent, followed by genotype 4, the latter mainly in African patients. The histological staging of liver disease conducted in 25 patients showed mild hepatitis in 13 subjects, moderate/severe hepatitis in eight subjects and cirrhosis in four. Although 45 out of 119 patients (37.8%) with determinable HCV RNA agreed to undergo treatment, 11 of them independently stopped taking medication before the course of therapy was completed, without any significant side effects. At the sixth month of follow-up, the overall sustained virological response (SVR) was shown by 22/45 patients (48.8%). In our study, migrant populations had higher rates of HCV-related chronic hepatitis than the indigenous population; in some cases the infections were contracted in the country of origin, but in others the infection took place in Italy. The most commonly represented genotype, besides 1, was 4, especially among Africans. The therapeutic management of immigrants proved to be very difficult, mostly but not exclusively because of social factors.

In children with type 1 diabetes mellitus (T1DM), elevated levels of antitissue transglutaminase (anti-tTG) antibody may spontaneously normalize, despite continued consumption of gluten. We aimed to investigate the prevalence of spontaneous normalization of anti-tTG levels and the existence of factors predictive for this outcome.

Obstructive sleep apnea syndrome (OSAS) in children can induce endothelial dysfunction, a well-known early marker of atherosclerosis. The study aimed to evaluate a link among endothelial function (measured by flow-mediated vasodilation (FMD)), obesity (evaluated by body mass index (BMI)), and sleep disordered breathing (SDB), assessed with apnoea/hypopnoea index (AHI), in a paediatric population. We demonstrated that our little OSAS patients showed an impaired endothelial function as compared to controls. In particular, the higher the AHI, the worst the FMD values and thus the endothelial function. Although the population sample is small, this study demonstrated that OSAS could impair endothelial function and worsen cardiovascular risk profile since childhood.

Celiac disease (CD) is an immune-mediated systemic disorder induced by a trigger factor in genetically susceptible individuals. There is emerging evidence about the impact of the month of birth on the development of several autoimmune diseases. Our aim was to investigate whether, in Italian CD children, the season of birth is associated with development of CD later in life. We report a survey conducted at two Italian referral centers for CD in Rome and Bari. The CD database was created to enable retrospective examination of the data of all the consecutive patients, born between 2003 and 2010, who had received a diagnosis of CD. This CD patient group comprising 596 children was compared with a reference group that included all subjects born in the same period and in the same cities (439,990 controls). Overall, there was a summer birth preponderance in CD patients compared to controls (28.2 % of CD patients vs 23.0 % of the control population; OR 1.315; 95 % CI 1.100 to 1.572). Stratifying the caseload by gender and age, the summer birth preponderance was maintained for females (28.6 % CD females vs 22.6 % control females; OR 1.368; 95 % CI 1.069 to 1.750).

Abstract IMPORTANCE: Recurrent abdominal pain is a prevalent health issue in childhood. Clinical criteria (ie, the Rome criteria) have been established to aid diagnosis. Studies of adults have shown an increased prevalence of celiac disease among patients with irritable bowel syndrome (IBS); few data are available with regard to children. OBJECTIVE: To assess the prevalence of celiac disease among children with abdominal pain-related functional gastrointestinal disorders classified according to the Rome criteria. DESIGN, SETTING, PARTICIPANTS: Six-year (2006-2012) prospective cohort study conducted in a tertiary referral center for the diagnosis and follow-up of gastrointestinal disorders in southern Italy (ie, Bari, Italy). A total of 992 children (42.8% male; median age, 6.8 years) consecutively referred for recurrent abdominal pain by their primary care physicians without previous investigation were evaluated. EXPOSURE: Patients were classified according to Rome III criteria as having IBS, functional dyspepsia, functional abdominal pain, or abdominal migraine. MAIN OUTCOMES AND MEASURES: Prevalence of celiac disease in each category of abdominal pain-related functional gastrointestinal disorder. Concentrations of IgA, IgA antitissue transglutaminase, and endomysial antibodies were measured, and a duodenal biopsy was performed in case of antibody positivity. RESULTS: A total of 992 children were evaluated: 270 were classified as having IBS, 201 as having functional dyspepsia, and 311 as having functional abdominal pain, and 210 children were excluded from the study because they had an organic disorder or some other functional gastrointestinal disorder (not related to abdominal pain). Serologic testing was performed for all 782 children included in the study, and 15 patients tested positive for celiac disease (12 of 270 patients with IBS [4.4%], 2 of 201 patients with functional dyspepsia [1%], and 1 of 311 patients with functional abdominal pain [0.3%]). Children presenting with IBS have a 4 times higher risk of having celiac disease than children without IBS (odds ratio, 4.19 [95% CI, 2.03-8.49]; P < .001). CONCLUSIONS AND RELEVANCE: The prevalence of celiac disease among children with IBS is 4 times higher than among the general pediatric population. Rome III classification of abdominal pain-related functional gastrointestinal disorders might help to select children who deserve screening for celiac disease.

Functional gastrointestinal disorders (FGIDs) are defined as a variable combination of chronic or recurrent gastrointestinal symptoms not explained by structural or biochemical abnormalities. Infantile colic, gastroesophageal reflux, and constipation are the most common FGIDs that lead to referral to a pediatrician during the first 6 months of life and are often responsible for hospitalization, feeding changes, use of drugs, parental anxiety, and loss of parental working days with relevant social consequences. We performed a retrospective study on patients referred for recurrent abdominal pain from January 2002 trough December 2009 to our Pediatric Gastroenterology Outpatient Unit. The population studied was matched with healthy control without history of recurrent abdominal pain, enrolled among pediatricians practicing primary health care. History of infantile colic, regurgitation, and functional constipation was detected respectively in 26.41, 25.31, and 30.16 % of children diagnosed with FGIDs compared to 11.34, 12.85, and 11.76 % of healthy children. Conclusion: According to our data, children with a history of gastrointestinal infantile distress have a higher prevalence of FGIDs years later.

BACKGROUND: Young infants are frequently affected by uncomplicated regurgitation that may persist despite dietetic and conservative interventions. On this basis, we studied the putative effects of probiotics on the frequency of regurgitation and gastric emptying time in infants with functional gastroesophageal reflux (GER). PATIENTS AND METHODS: Forty-two infants with regurgitation were randomized to assume Lactobacillus reuteri DSM 17938 at a dose of 1 × 10(8) CFU per day and placebo for 30 days. The episodes of regurgitation were recorded by the parents each day. Gastric emptying time was recorded using real-time ultrasound at baseline and at the end of the study. Twenty-one infants without regurgitation were enroled to compare anthropometric and physiological parameters before the intervention diet. RESULTS: Thirty-four infants completed the study (19 infants receiving probiotics and 15 placebo).At baseline, the whole group of infants was similar to the control group as regards anthropometric and physiological data. The median fasting antral area was significantly reduced, (P = 0·01) the delta in gastric emptying rate was significantly increased (P = 0·01) and the median episodes per day of regurgitation was reduced (, P < 0·001) in the probiotic group compared to the placebo group. In the whole group, the frequency of regurgitation and the basal antral area showed a positive correlation (r = 0·53, P = 0·004). CONCLUSIONS: In infants with functional GER, L. reuteri DSM 17938 reduce gastric distension and accelerate gastric emptying. In addition, this probiotic strain seems to diminish the frequency of regurgitation.

GOALS:: The goals of this study were to investigate the role of a new probiotic preparation (Lactobacillus reuteri DSM 17938 and L. reuteri ATCC PTA 6475) in Helicobacter pylori infection. BACKGROUND:: Specific probiotic strains play a role in H. pylori infection for their ability to decrease bacterial load and gastritis, prevent antibiotic-associated side effects, and increase the eradication rate. STUDY:: This is a prospective, double-blind, randomized, placebo-controlled study in a tertiary care setting. A total of 100 H. pylori-positive naive patients received either L. reuteri combination (2×10 Colony Forming Units) or placebo during a 3-phase study (pre-eradication, eradication, and follow-up). All underwent C urea breath test (C-UBT), blood assessments of gastrin-17 (G17), endoscopy, and the Gastrointestinal Symptom Rating Scale. Eradication was confirmed by C-UBT 8 weeks after the completion of therapy. RESULTS:: Fifty patients were allocated in each group. During pre-eradication period, C-UBT δ decreased by 13% in L. reuteri combination as compared with a 4% increase in placebo (-13.2±34% vs. 4.3±27%; P<0.03). During eradication, GSRS increased significantly in placebo as compared with L. reuteri combination (6.8±2.9 vs. 4±3.1; P<0.01). Significantly less patients in L. reuteri combination as compared with placebo-reported side effects (40.9% vs. 62.8%; P<0.04). An abnormal G17 value was found in patients receiving placebo as compared with L. reuteri combination (28% vs. 12%; P<0.02). Eradication rate was 75% in L. reuteri combination and 65.9% in placebo (P=NS). L. reuteri combination increased eradication rate by 9.1% (odds ratio: 1.5). CONCLUSIONS:: L. reuteri combination alone is able to exert an inhibitory effect on H. pylori growth, and when administered with eradication therapy, it determines a significant reduction in antibiotic-associated side effects. Moreover, L. reuteri combination was able to decrease serum G17 levels and to (not significantly) increase the H. pylori-eradication rate.

BACKGROUND/AIMS: The aim of this study was to investigate the alterations in the oxidant/antioxidant status in obese children with and without metabolic syndrome (MetS). METHODS: We recruited 25 Caucasian obese children with MetS, 30 Caucasian children with simple obesity and a control group of 30 Caucasian children. We performed diacron-reactive oxygen metabolites (d-ROMs) test and biological antioxidant potential (BAP) test in order to evaluate the oxidant-antioxidant status in recruited patients. RESULTS: d-ROM level was significantly higher in obese children with and without MetS (p = 0.005). The total antioxidant capacity (BAP level) was reduced in MetS and noMetS children compared to controls (p = 0.009). The subjects without MetS had higher d-ROMs test and lower BAP/d-ROMs ratio than subjects with MetS (although not significant). The ratio BAP/d-ROMs was higher in controls than noMetS and MetS children (p < 0.0001). d-ROM level was higher in prepubertal subjects with MetS than pubertal ones (p = 0.03). A direct correlation was found between d-ROM levels and BMI SDS (p = 0.0005), while an inverse correlation was found between BAP and BMI SDS (p = 0.004) and BAP/d-ROMs and BMI SDS (p = 0.0001). CONCLUSIONS: This result confirms that fat accumulation plays a key role in the pathogenesis of systemic oxidative stress already during pediatric age.

To provide an overview on the role of gut immunity, nervous system and motility patterns in the development of feeding intolerance in newborns. Maturation of the GI is important not only for digestion and absorption, but for endocrine and exocrine function as well. There is little data available about the development of the motility function and of the mucosal barrier of the human gut, and in particular about the motility patterns and mucosal changes in newborns during early days of life. It is known that functional maturation of the gastrointestinal tract is quite different over time with respect to its anatomical development. Besides, the gastrointestinal tract through innate and specific immunologic factors, acts as a defense against ingested antigens. In addition to the mucous membrane integrity and digestion, numerous specific immunologic cells and mediators orchestrate such defensive mechanisms. In case of food antigens, the outcome is usually in favor of tolerance. Defects in that barrier, however, can lead to the development of aberrant immunologic responses, including hypersensitivity reactions. It is obvious that an appropriate feeding regimen during early infancy is in favor of food tolerance. However, in addition to genetic predisposition, development of tolerance is facilitated by an adequate gut barrier (immune or nonimmune), well-coordinated GI motility and nervous network, and appropriate food regimen.

Approximately 50 percent of the world population is infected with Helicobacter pylori (H. pylori), with the highest prevalence rates in developing countries. The current guidelines suggest the use of triple therapy as first choice treatment of Helicobacter pylori infection, although the eradication failure rate is more than 30 percent. Current interest in probiotics as therapeutic agents against Helicobacter pylori is stimulated by the increasing resistance of pathogenic bacteria to antibiotics, thus the interest for alternative therapies is a real actual topic. Available data in children indicate that probiotics seem to be efficacious for the prevention of antibiotic associated side-effects, and might be of help for the prevention of Helicobacter pylori complications by decreasing Helicobacter pylori density and gastritis, and for the prevention of Helicobacter pylori colonization or re-infection by inhibiting adhesion to gastric epithelial cells. There is no clear evidence that probiotics may increase the Helicobacter pylori eradication rate.

Abstract Background/Aims: Prolactin (PRL) is produced by the anterior pituitary gland. It exerts its role on the breast gland but also plays a modulatory role in autoimmune mechanisms. Celiac disease (CD) is a gluten-sensitive autoimmune enteropathy sometimes associated with autoimmune endocrinopathies. No data on PRL levels in CD patients are available at diagnosis, and no conclusive data are reported. Methods: We aimed to evaluate PRL secretion in newly diagnosed CD pediatric patients and, in the case of hyperprolactinemia, any changes in its levels while the patients were on a gluten-free diet (GFD). We recruited 67 patients and 39 healthy controls. Results: PRL was statistically higher in the CD patients (13.5 ± 9.2 ng/ml) than in the controls (8.5 ± 5.0 ng/ml). In the CD group, PRL was inversely correlated with the age at diagnosis (r = -0.326; p = 0.007). In patients with hyperprolactinemia at diagnosis, PRL decreased after 6 months of GFD. Conclusion: This paper confirms that PRL may be increased at diagnosis of CD and shows, for the first time, that it decreases after a short course of GFD. Changes in the levels of inflammatory cytokines in CD may account for changes in PRL levels. Younger patients seem more prone to develop hyperprolactinemia than older ones.

BACKGROUND: Probiotics may be of help for the management of acute diarrhoea, however, the effect is strain specific and efficacy needs to be proven. AIM: To test the efficacy and safety of Lactobacillus reuteri DSM 17938 derived from L. reuteri ATCC 55730 in children with acute diarrhoea. Primary outcomes were the rate of unresolved diarrhoea after 3 days of treatment and duration of diarrhoea. METHODS: Children (6-36 months), hospitalised in three paediatric hospitals in Southern Italy for acute diarrhoea with clinical signs of dehydration were randomised to receive in a double-blind fashion either L. reuteri (dose of 4 × 10(8) colony-forming units/die) or placebo. RESULTS: Out of 96 eligible children, 74 were enrolled, five patients were withdrawn; 35 in the L. reuteri group and 34 in the placebo group. Lactobacillus reuteri significantly reduced the duration of watery diarrhoea as compared with placebo (2.1 ± 1.7 days vs. 3.3 ± 2.1 days; P < 0.03); on day two and three of treatment watery diarrhoea persisted in 82% and 74% of the placebo and 55% and 45% of the L. reuteri recipients respectively (P < 0.01; P < 0.03). Finally, children receiving L. reuteri had a significantly lower relapse rate of diarrhoea (15% vs. 42%; P < 0.03). There was not a significant difference in hospital stay between the groups. No adverse events were recorded. CONCLUSION: Our study shows that L . reuteri DSM 17938 as an adjunct to rehydration therapy is efficacious in the treatment of acute diarrhoea reducing the frequency, duration and recrudescence rate of the disease.

To evaluate the long-term validity and safety of pure oats in the treatment of children with celiac disease.

The aim of the present work was to assess the prevalence of early cardiac involvement in children with celiac disease (CD), and the impact of a gluten free diet (GFD) on this issue. Sixty CD children was compared with a control group of 45 healthy children by an echocardiographic examination. CD patients were re-evaluated 1-year after 1-year GFD. Main outcome measures were ejection fraction (EF), fractional shortening (FS), left ventricular end-diastolic diameter (LVDD), left ventricular end-systolic diameter (LVSD), any regurgitating valve lesions. Mild cardiac involvement was found in 13 CD children and in one control (21.7% vs. 2.2%; p=0.003), and was secondary to regurgitation of mitral valve, aortic valve, pulmonary and tricuspid valve, or to impaired ejection fraction. CD children as compared to controls had significantly lower contractility indices, and higher left ventricular dimensions. In patients adhering to the GFD all valve regurgitations resolved, and the echocardiographic parameters significantly improved. Subclinical cardiac involvement in CD children is quite frequent, and GFD may exert a beneficial effect on the overall cardiac performance.

Abstract Abstract Objective: A supervised multivariate model to classify the metabolome alterations between autistic spectrum disorders (ASD) patients and controls, siblings of autistic patients, has been realized and used to realize a network model of the ASD patients' metabolome. METHODS: In our experiment we propose a quantification of urinary metabolites with the Mass Spectroscopy technique couple to Gas Chromatography. A multivariate model has been used to extrapolate the variables of importance for a network model of interaction between metabolites. In this way we are able to propose a network-based approach to ASD description. RESULTS: Children with autistic disease composing our studied population showed elevated concentration of several organic acids and sugars. Interactions among diet, intestinal flora and genes may explain such findings. Among them, the 3-(3-hydroxyphenyl)-3-hydroxypropanoic acid has been previously described as altered in autistic subjects. Other metabolites increased are 3,4-dihydroxybutyric acid, glycolic acid and glycine, cis-aconitic acid; phenylalanine, tyrosine, p-hydroxyphenylacetic acid, and homovanillic acid are all involved in the tyrosine pathway leading to neurotransmitter cathecolamine. CONCLUSION: GC-MS-based metabolomic analysis of the urinary metabolome suggests to have the required sensitivity and specificity to gain insight into ASD phenotypes and aid a personalized network-based medicine approach.

Gluten-free diet (GFD) is the cornerstone treatment for celiac disease (CD). This diet excludes the protein gluten a protein forum in in grains such as wheat, barley, rye and triticale. Gluten causes small intestines inflammation in patients with CD and eating a GFD helps these patients in controlling signs and symptoms and prevent complications. Following a GFD may be frustrating, however, it is important to know that plenty of foods are naturally gluten-free and nowadays is relatively easy to find substitutes for gluten-containing foods. Certain grains, such as oats, are generally safe but can be contaminated with wheat during growing and processing stages of production. For this reason, it is generally recommended avoiding oats unless they are specifically labelled gluten-free. Other products that may contain gluten include food additives, such as malt flavouring, modified food starch and some supplement and/or vitamins that use gluten as a binding agent. Cross-contamination occurs when gluten-free foods come into contact with foods that contain gluten. It can happen during the manufacturing process or if the same equipment is used to make a variety of products. Cross-contamination can also occur at home if foods are prepared on common surfaces or with utensils that have not been cleaned after being used to prepare gluten-containing foods (using a toaster for gluten-free and regular bread). Although safe and effective, the GFD is not ideal: it is expensive, of limited nutritional value, and not readily available in many countries. Consequently, a need exists for novel, non-dietary therapies for celiac disease. Advances in understanding the immunopathogenesis of CD have suggested several types of therapeutic strategies alternative to the GFD. Some of these strategies attempt to decrease the immunogenicity of gluten-containing grains by manipulating the grain itself or by using oral enzymes to break down immunogenic peptides that normally remain intact during digestion. Other strategies focus on preventing the absorption of these peptides, preventing tissue transglutaminase from rendering gluten peptides more immunogenic, or inhibiting their binding to CD-specific antigen-presenting molecules. Strategies that limit T cell migration to the small intestine or that re-establish mucosal homeostasis and tolerance to gluten antigens are also being explored.

Gullo's syndrome is a newly identified condition characterized by a chronic elevation of pancreatic amylase and/or lipase in the absence of pancreatic disease. Until now, only one case of benign isolated hyperlipasemia in children has been recorded. We describe two children with benign and not familial increase of serum lipase. Case 1: a six year old girl presented with occasional discovery of serum lipase elevation. Medical history was silent for pancreatic hyperenzymemia. The screening for possible causes for elevated lipase (genetic, autoimmune and infectious diseases) was normal. The serum lipase increased three fold over the upper limit (193 U/L; reference range 0-60 U/L), with daily fluctuation of values. Both ultrasound scan and magnetic resonance imaging were normal. The genetic mutation associated with chronic pancreatitis was negative. We followed up this patient for two years with blood tests every six months and she did not show any signs or symptoms of pancreatic disease, except for the high level of lipase serum. Case 2: an eight year old girl complained of nausea, vomiting and severe abdominal pain in the epigastric region after eating for the last two weeks. Full blood count, electrolytes, C-reactive protein, liver and renal function were normal. Serum lipase was 96 U/L (reference range 0-60 U/L). The screening for the possible causes of pancreatic disease was negative. Endoscopy of the upper gastrointestinal tract, ultrasound, computed tomography scan and magnetic resonance imaging were normal. One year after the presentation of the symptoms, the patient became asymptomatic although the level of serum lipase continued to be high.